Genomic architecture of phenotypic extremes in a wild cervid.

Identifying the genes underlying fitness-related traits such as body size and male ornamentation can provide tools for conservation and management and are often subject to various selective pressures. Here we performed high-depth whole genome re-sequencing of pools of individuals representing the phenotypic extremes for antler and body size in white-tailed deer (Odocoileus virginianus). Samples were selected from a tissue repository containing phenotypic data for 4,466 male white-tailed deer from Anticosti Island, Quebec, with four pools representing the extreme phenotypes for antler and body size after controlling for age. Our results revealed a largely homogenous population but detected highly divergent windows between pools for both traits, with the mean allele frequency difference of 14% for and 13% for antler and body SNPs in outlier windows, respectively. Genes in outlier antler windows were enriched for pathways associated with cell death and protein metabolism and some of the most differentiated windows included genes associated with oncogenic pathways and reproduction, processes consistent with antler evolution and growth. Genes associated with body size were more nuanced, suggestive of a highly complex trait. Overall, this study revealed the complex genomic make-up of both antler morphology and body size in free-ranging white-tailed deer and identified target loci for additional analyses.

Subtle changes in crosslinking drive diverse anomalous transport characteristics in actin-microtubule networks.

Anomalous diffusion in crowded and complex environments is widely studied due to its importance in intracellular transport, fluid rheology and materials engineering. Specifically, diffusion through the cytoskeleton, a network comprised of semiflexible actin filaments and rigid microtubules that interact both sterically and via crosslinking, plays a principal role in viral infection, vesicle transport and targeted drug delivery. Here, we elucidate the impact of crosslinking on particle diffusion in composites of actin and microtubules with actin-actin, microtubule-microtubule and actin-microtubule crosslinking. We analyze a suite of transport metrics by coupling single-particle tracking and differential dynamic microscopy. Using these complementary techniques, we find that particles display non-Gaussian and non-ergodic subdiffusion that is markedly enhanced by cytoskeletal crosslinking, which we attribute to suppressed microtubule mobility. However, the extent to which transport deviates from normal Brownian diffusion depends strongly on the crosslinking motif - with actin-microtubule crosslinking inducing the most pronounced anomalous characteristics. Our results reveal that subtle changes to actin-microtubule interactions can have complex impacts on particle diffusion in cytoskeleton composites, and suggest that a combination of reduced filament mobility and more variance in actin mobilities leads to more strongly anomalous particle transport.

Late-life depression and increased risk of dementia: a longitudinal cohort study.

Late-life depression (LLD) is associated with an increased risk of developing dementia; however, it is not known whether individuals with a history of LLD exhibit a more rapid rate of cognitive decline. We aimed to determine whether those with LLD experienced faster cognitive decline compared with never-depressed control (NDC) participants from the community and whether stratification of LLD into early-onset depression (EOD) and late-onset depression (LOD) subtypes revealed differing rates and domain-specific expression of cognitive decline. We conducted a prospective, longitudinal study where 185 participants with LLD (remitted) and 114 NDC were followed for 5 years on average. EOD was defined as having first lifetime depressive episode at <60years and LOD at ≥60years. Every year, participants underwent comprehensive neuropsychological assessment. Composite scores for each cognitive domain were calculated through averaging standardized scores across tests. LLD compared to NDC demonstrated significant baseline impairment but did not decline more rapidly. EOD were significantly impaired in attention/processing speed and global cognitive function at baseline but did not experience more rapid decline as compared to NDC. Those with LOD compared to both NDC and EOD performed worse in all domains at baseline and experienced more rapid decline in verbal skills and delayed memory ability. Our findings suggest that baseline impairment may lower the threshold for those with LLD to develop dementia. EOD and LOD may represent distinct phenotypes of cognitive impairment with differing neural substrates. LOD may represent a distinct phenotype with a more rapid decline in verbal skills and delayed memory.

Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline.

IMPORTANCE: Adults with Down syndrome (DS) are at high-risk of revealing Alzheimer's disease (AD) pathology, in part due to the triplication of chromosome 21 encoding the amyloid precursor protein. Adults with DS are uniformly affected by AD pathology by their 30's and have a 70% to 80% chance of clinical dementia by their 60's. Our previous studies have assessed longitudinal changes in amyloid beta (Aß) accumulation in DS. OBJECTIVE: The goal of the present study was to assess the presence of brain tau using [18F]AV-1451 positron emission tomography (PET) in DS and to assess the relationship of brain tau pathology to Aß using Pittsburgh Compound B (PiB)-PET. DESIGN: Cohort study. SETTING: Multi-center study. PARTICIPANTS: Participants consisted of a sample of individuals with DS and sibling controls recruited from the community; exclusion criteria included contraindications for magnetic resonance imaging (MRI) and/or a medical or psychiatric condition that impaired cognitive functioning. EXPOSURES: PET brain scans to assess Aß ([11C]PiB) and tau ([18F]AV-1451) burden. MAIN OUTCOMES AND MEASURES: Multiple linear regression models (adjusted for chronological age, sex and performance site) were used to examine associations between regional [18F]AV-1451 standard uptake value ratio (SUVR) (based on regions associated with Braak stages 1-6) and global [11C]PiB SUVR (as both a continuous and dichotomous variable). RESULTS: A cohort of 156 participants (mean age = 39.05, SD(8.4)) were examined. These results revealed a significant relationship between in vivo Aß and tau pathology in DS. As a dichotomous variable, [18F]AV-1451 retention was higher in each Braak region in PiB(+) participants. We also found, based on our statistical models, starting with the Braak 3 region of interest (ROI), an acceleration of [18F]AV-1451 SUVR deposition with [11C]PiB SUVR increases.

Loss of end-differentiated ß-cell phenotype following pancreatic islet transplantation.

Replacement of pancreatic ß-cells through deceased donor islet transplantation is a proven therapy for preventing recurrent life-threatening hypoglycemia in type 1 diabetes. Although near-normal glucose levels and insulin independence can be maintained for many years following successful islet transplantation, restoration of normal functional ß-cell mass has remained elusive. It has recently been proposed that dedifferentiation/plasticity towards other endocrine phenotypes may play an important role in stress-induced ß-cell dysfunction in type 2 diabetes. Here we report loss of end-differentiated ß-cell phenotype in 2 intraportal islet allotransplant recipients. Despite excellent graft function and sustained insulin independence, all examined insulin-positive cells had lost expression of the end-differentiation marker, urocortin-3, or appeared to co-express the α-cell marker, glucagon. In contrast, no insulin+ /urocortin-3- cells were seen in nondiabetic deceased donor control pancreatic islets. Loss of end-differentiated phenotype may facilitate ß-cell survival during the stresses associated with islet isolation and culture, in addition to sustained hypoxia following engraftment. As further refinements in islet isolation and culture are made in parallel with exploration of alternative ß-cell sources, graft sites, and ultimately fully vascularized bioengineered insulin-secreting microtissues, differentiation status immunostaining provides a novel tool to assess whether fully mature ß-cell phenotype has been maintained.

Improving public health intervention for mosquito-borne disease: the value of geovisualization using source of infection and LandScan data.

Epidemiological studies use georeferenced health data to identify disease clusters but the accuracy of this georeferencing is obfuscated by incorrectly assigning the source of infection and by aggregating case data to larger geographical areas. Often, place of residence (residence) is used as a proxy for the source of infection (source) which may not be accurate. Using a 21-year dataset from South Australia of human infections with the mosquito-borne Ross River virus, we found that 37% of cases were believed to have been acquired away from home. We constructed two risk maps using age-standardized morbidity ratios (SMRs) calculated using residence and patient-reported source. Both maps confirm significant inter-suburb variation in SMRs. Areas frequently named as the source (but not residence) and the highest-risk suburbs both tend to be tourist locations with vector mosquito habitat, and camping or outdoor recreational opportunities. We suggest the highest-risk suburbs as places to focus on for disease control measures. We also use a novel application of ambient population data (LandScan) to improve the interpretation of these risk maps and propose how this approach can aid in implementing disease abatement measures on a smaller scale than for which disease data are available.

Real-Time PCR Assay for Detection of Sphacelotheca reiliana Infection in Maize (Zea mays) Seedlings and Evaluation of Seed Treatment Efficacy.

Head smut of maize, caused by the fungus Sphacelotheca reiliana, is an economically important disease in all major maize-producing countries. Although seed treatments are commonly used for management purposes, evaluating these treatments for efficacy is both time consuming and inefficient. Therefore, in order to improve the capacity for evaluating seed treatment fungicides, we developed a real-time PCR-based seedling assay for S. reiliana infection. We optimized growth chamber conditions and inoculation methods to achieve infection incidence of 60 to 80% in inoculated, nontreated controls. The effects of five commercially available fungicidal seed treatment formulations on seedling infection incidence were compared by PCR analysis of root and mesocotyl tissues. Tebuconazole, fludioxonil, sedaxane, and Maxim Quattro (fludioxonil+mefenoxam+azoxystrobin+thiabendazole) reduced the incidence of infection (P < 0.05) compared with the control, but no difference was found between the azoxystrobin treatment and the control. All rates tested for both sedaxane and tebuconazole were equally effective for seeds coated with 106 teliospores∙seed-1. Sedaxane, at a rate of 0.1 mg/kernel, eliminated seedling infection if seeds were infested with a low inoculum concentration (101 teliospores∙seed-1). The assay developed here is a valuable tool not only for the detection of fungal infection at the seedling stage, but also for testing the relative efficacies of seed treatments for reducing incidence of infection.

Two-year course of cognitive function and instrumental activities of daily living in older adults with bipolar disorder: evidence for neuroprogression?

BACKGROUND: While bipolar disorder (BD) is a leading cause of disability, and an important contributor to disability in BD is cognitive impairment, there is little systematic research on the longitudinal course of cognitive function and instrumental activities of daily living (IADLs) in late-life. In this report, we characterize the 2-year course of cognitive function and IADLs in older adults with BD. Method We recruited non-demented individuals 50 years and older with BD I or BD II (n = 47) from out-patient clinics or treatment studies at the University of Pittsburgh. Comparator subjects ('controls') were 22 individuals of comparable age and education with no psychiatric or neurologic history, but similar levels of cardiovascular disease. We assessed cognitive function and IADLs at baseline, 1- and 2-year time-points. The neuropsychological evaluation comprised 21 well-established and validated tests assessing multiple cognitive domains. We assessed IADLs using a criterion-referenced, performance-based instrument. We employed repeated-measures mixed-effects linear models to examine trajectory of cognitive function. We employed non-parametric tests for analysis of IADLs. RESULTS: The BD group displayed worse cognitive function in all domains and worse IADL performance than the comparator group at baseline and over follow-up. Global cognitive function and IADLs were correlated at all time-points. The BD group did not exhibit accelerated cognitive decline over 2 years. CONCLUSIONS: Over 2 years, cognitive impairment and associated functional disability of older adults with BD appear to be due to long-standing neuroprogressive processes compounded by normal cognitive aging rather than accelerated cognitive loss in old age.

The role of oscillatory brain activity in object processing and figure-ground segmentation in human vision.

The perception of an object as a single entity within a visual scene requires that its features are bound together and segregated from the background and/or other objects. Here, we used magnetoencephalography (MEG) to assess the hypothesis that coherent percepts may arise from the synchronized high frequency (gamma) activity between neurons that code features of the same object. We also assessed the role of low frequency (alpha, beta) activity in object processing. The target stimulus (i.e. object) was a small patch of a concentric grating of 3c/°, viewed eccentrically. The background stimulus was either a blank field or a concentric grating of 3c/° periodicity, viewed centrally. With patterned backgrounds, the target stimulus emerged--through rotation about its own centre--as a circular subsection of the background. Data were acquired using a 275-channel whole-head MEG system and analyzed using Synthetic Aperture Magnetometry (SAM), which allows one to generate images of task-related cortical oscillatory power changes within specific frequency bands. Significant oscillatory activity across a broad range of frequencies was evident at the V1/V2 border, and subsequent analyses were based on a virtual electrode at this location. When the target was presented in isolation, we observed that: (i) contralateral stimulation yielded a sustained power increase in gamma activity; and (ii) both contra- and ipsilateral stimulation yielded near identical transient power changes in alpha (and beta) activity. When the target was presented against a patterned background, we observed that: (i) contralateral stimulation yielded an increase in high-gamma (>55 Hz) power together with a decrease in low-gamma (40-55 Hz) power; and (ii) both contra- and ipsilateral stimulation yielded a transient decrease in alpha (and beta) activity, though the reduction tended to be greatest for contralateral stimulation. The opposing power changes across different regions of the gamma spectrum with 'figure/ground' stimulation suggest a possible dual role for gamma rhythms in visual object coding, and provide general support of the binding-by-synchronization hypothesis. As the power changes in alpha and beta activity were largely independent of the spatial location of the target, however, we conclude that their role in object processing may relate principally to changes in visual attention.

Cortical oscillatory activity associated with the perception of illusory and real visual contours.

We used magnetoencephalography (MEG) to examine the nature of oscillatory brain rhythms when passively viewing both illusory and real visual contours. Three stimuli were employed: a Kanizsa triangle; a Kanizsa triangle with a real triangular contour superimposed; and a control figure in which the corner elements used to form the Kanizsa triangle were rotated to negate the formation of illusory contours. The MEG data were analysed using synthetic aperture magnetometry (SAM) to enable the spatial localisation of task-related oscillatory power changes within specific frequency bands, and the time-course of activity within given locations-of-interest was determined by calculating time-frequency plots using a Morlet wavelet transform. In contrast to earlier studies, we did not find increases in gamma activity (>30 Hz) to illusory shapes, but instead a decrease in 10-30 Hz activity approximately 200 ms after stimulus presentation. The reduction in oscillatory activity was primarily evident within extrastriate areas, including the lateral occipital complex (LOC). Importantly, this same pattern of results was evident for each stimulus type. Our results further highlight the importance of the LOC and a network of posterior brain regions in processing visual contours, be they illusory or real in nature. The similarity of the results for both real and illusory contours, however, leads us to conclude that the broadband (<30 Hz) decrease in power we observed is more likely to reflect general changes in visual attention than neural computations specific to processing visual contours.

"And they told two friends...and so on": RJ Reynolds' viral marketing of Eclipse and its potential to mislead the public.

OBJECTIVE: To explore viral marketing strategies for Eclipse cigarettes used by the RJ Reynolds Company (Winston-Salem, North Carolina, USA). METHODS: Analysis of previously secret tobacco industry documents and multimedia materials. RESULTS: The failure of RJ Reynolds' (RJR) 1988 "smokeless" cigarette, Premier, was in part due to widespread bad word of mouth about the product's flavour, quality and difficulty of use. In 1994 RJR introduced an updated version of Premier, the ostensibly "reduced risk" Eclipse cigarette. RJR developed viral marketing channels to promote Eclipse using (1) exploratory interviews to motivate consumers to spread the word about Eclipse prior to market release, (2) promotional videos featuring positive feedback from test group participants to portray majority consensus among triers, (3) "Tupperware"-like parties for Eclipse where participants received samples to pass around in their social circles and (4) the Eclipse website's bulletin board as a forum for potential users to discuss the brand in their own words. These strategies targeted the brand's likeliest adopters, recruited informal and credible representatives of the product unaffiliated with RJR, and controlled the information spread about the product. CONCLUSIONS: Viral marketing techniques may be particularly useful to promote new tobacco products such as Eclipse that have limited appeal and need a highly motivated audience of early adopters and acceptors. Such techniques help evade the mass rejection that could follow mass promotion, circumvent marketing restrictions, and allow tobacco companies to benefit from health claims made by consumers. Cigarette manufacturers must be held accountable for perceived health benefits encouraged by all promotional activities including viral marketing.

A common pathway toward women's health.

This paper calls for an alternate approach to studying the aetiology of women's health conditions. Instead of the long-established disease-specific, compartmentalized approach, it recommends focusing on risk exposures that allows for the identification of multiple disease conditions that stem from the same risk factors. Identifying common risk factors and the related pathways to adverse health outcomes can lead to the development of interventions that would favourably affect more than one disease condition. The utility of such an approach is illustrated by a review of literature from across the globe on the association between gender inequity-related exposures and women's health (namely, three health conditions: sexually transmitted infections [STIs], including Human Immunodeficiency Virus [HIV], blindness, and depression; as well as two risk behaviours: eating disorders and tobacco use). The review demonstrates how women's health cannot be viewed independently from the larger social, economic, and political context in which women are situated. Promoting women's health necessitates more comprehensive approaches, such as gender-sensitization of other family members, and the development of more creative and flexible mechanisms of healthcare delivery, that acknowledge the gender inequity-related constraints that women face in their daily lives.

A preliminary investigation of the reliability and validity of the Brief Assessment Schedule Depression Cards and the Beck Depression Inventory-Fast Screen to screen for depression in older stroke survivors.

OBJECTIVE: To conduct an initial assessment of the reliability and validity of the Brief Assessment Schedule Depression Cards (BASDEC) and the Beck Depression Inventory-Fast Screen (BDI-FS) to screen for depression in older stroke survivors. METHODS: Participants from four inpatient rehabilitation units completed the BASDEC and the BDI-FS together with the Hospital Anxiety and Depression Scale (HADS) for comparison. The Structured Clinical Interview for DSM-IV Axis 1 Disorders (SCID) was then completed with all participants to ascertain a criterion depression diagnosis. The BASDEC and BDI-FS were subsequently completed for a second time. RESULTS: Forty-nine stroke survivors (M=78.80, SD=6.79 years) were included. The BASDEC and BDI-FS demonstrated acceptable internal consistency and test-retest reliability. The BASDEC (cut-off >or=7) resulted in a sensitivity of 1.0 and specificity of 0.95 for detecting major depression whereas the BDI-FS (cut-off >or=4) had a sensitivity of 0.71 and specificity of 0.74. When participants with minor depression were included in analyses, sensitivity lowered to 0.69 (specificity=0.97) for the BASDEC and 0.62 (specificity=0.78) for the BDI-FS. CONCLUSIONS: The BASDEC and BDI-FS were found to have acceptable reliability. The BASDEC demonstrated some advantage in criterion validity over the BDI-FS at the examined cut-offs.

Microsatellite flanking region similarities among different loci within insect species.

Although microsatellites are ubiquitous in eukaryota, the number of available markers varies strongly among taxa. This meta-analysis was conducted on 32 insect species. Sequences were obtained from two assembled whole genomes, whole genome shotgun (WGS) sequences from 10 species and screening partial genomic libraries for microsatellites from 23 species. We have demonstrated: (1) strong differences in the abundance of microsatellites among species; (2) that microsatellites within species are often grouped into families based on similarities in their flanking sequences; (3) that the proportion of microsatellites grouped into families varies strongly among taxa; and (4) that microsatellite families were significantly more often associated with transposable elements - or their remnants - than unique microsatellite sequences.

Every document and picture tells a story: using internal corporate document reviews, semiotics, and content analysis to assess tobacco advertising.

In this article we present communication theory as a conceptual framework for conducting documents research on tobacco advertising strategies, and we discuss two methods for analysing advertisements: semiotics and content analysis. We provide concrete examples of how we have used tobacco industry documents archives and tobacco advertisement collections iteratively in our research to yield a synergistic analysis of these two complementary data sources. Tobacco promotion researchers should consider adopting these theoretical and methodological approaches.

Effect of age related macular degeneration on the Eger macular stressometer photostress recovery time.

AIM: To assess the repeatability of Eger macular stressometer (EMS) measures of photostress recovery and determine their association with other measures of visual function. METHODS: EMS photostress recovery time was measured in 90 patients with bilateral exudative age related macular degeneration (AMD), 19 with bilateral atrophic AMD and 47 with both forms of the condition (mean age 79 (SD 13) years). Measurements were made on two occasions separated by 1 year. Intrasession repeatability was assessed by repeating the measures after a 10 minute recovery period at the first visit. Distance visual acuity was measured with a logMAR chart, near visual acuity with a MNRead chart at 25 cm, contrast sensitivity with a Pelli-Robson chart, and the presence of central visual disturbance assessed with an Amsler grid. A questionnaire was used to assess self reported difficulties with glare recovery. RESULTS: The average EMS recovery time was 11.0 (SD 8.9) seconds, decreasing by 1.6 (5.2) seconds on repeated measurement (p<0.05). EMS photostress recovery was not correlated with visual function measures or subjective difficulties with lights (p>0.05). EMS photostress recovery time did not predict those whose vision decreased over the following year compared with those among whom it remained stable. CONCLUSIONS: The EMS test is not a useful tool in determining the severity or progression of AMD.

Emotions for sale: cigarette advertising and women's psychosocial needs.

OBJECTIVE: To explore messages of psychosocial needs satisfaction in cigarette advertising targeting women and implications for tobacco control policy. METHODS: Analysis of internal tobacco industry documents and public advertising collections. RESULTS: Tobacco industry market research attempted to identify the psychosocial needs of different groups of women, and cigarette advertising campaigns for brands that women smoke explicitly aimed to position cigarettes as capable of satisfying these needs. Such positioning can be accomplished with advertising that downplays or excludes smoking imagery. As women's needs change with age and over time, advertisements were developed to reflect the needs encountered at different stages in women's lives. Cigarette brands for younger women stressed female camaraderie, self confidence, freedom, and independence; cigarette brands for older women addressed needs for pleasure, relaxation, social acceptability, and escape from daily stresses. CONCLUSIONS: Psychosocial needs satisfaction can be communicated without reference to cigarettes or smoking. This may explain why partial advertising bans are ineffective and comprehensive bans on all forms of tobacco marketing are effective. Counter-advertising should attempt to expose and undermine the needs satisfaction messages of cigarette advertising campaigns directed at women.

Perceived quality of health care in macular disease: a survey of members of the Macular Disease Society.

AIM: To investigate the experiences of people with macular disease within the British healthcare system. METHOD: The Macular Disease Society Questionnaire, a self completion questionnaire designed to survey the experiences of people with macular disease, was sent to 2000 randomly selected members of the Macular Disease Society. The questionnaire incorporated items about people's experiences with health professionals and the information and support provided by them at the time of diagnosis and thereafter. RESULTS: Over 50% thought their consultant eye specialist was not interested in them as a person and 40% were dissatisfied with their diagnostic consultation. 185 people thought their general practitioner (GP) was well informed about macular disease but twice as many people thought their GP was not well informed. About an equal number of people thought their GP was supportive as those who thought their GP was not supportive. A total of 1247 people were told "nothing can be done to help with your macular disease." A number of negative emotional reactions were experienced by those people as a result, with 61% of them reporting feeling anxious or depressed. Of 282 people experiencing visual hallucinations after diagnosis with macular disease, only 20.9% were offered explanations for them. CONCLUSIONS: Many people with macular disease have unsatisfactory experiences of the healthcare system. Many of the reasons for dissatisfaction could be resolved by healthcare professionals if they were better informed about macular disease and had a better understanding of and empathy with patients' experiences.